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Biomedical subjects

P Knudsen

Publications and source records attributed to P Knudsen.

34 records · Page 2Linked to original sources
PubMed1985

Pharmacokinetic implications of different oil vehicles used in depot neuroleptic treatment.

On separate occasions two male schizophrenic inpatients were given intramuscular injections of equal amounts of perphenazine decanoate dissolved in sesame oil and Viscoleo, respectively. Substantially more even, but also lower perphenazine plasma concentrations were found within the dose intervals following the injections of perphenazine decanoate dissolved in sesame oil compared to the intervals following the Viscoleo-preparation. The occurrence of extrapyramidal side effects were consistent with the magnitude of the perphenazine plasma concentrations. The results support the importance of selecting an appropriate oil vehicle in a depot neuroleptic.

Adult↗
PubMed1985

Perphenazine decanoate in sesame oil vs. perphenazine enanthate in sesame oil: a comparative study of pharmacokinetic properties and some clinical implications.

Ten schizophrenic inpatients were each treated with perphenazine enanthate (PE) and perphenazine decanoate (PD). Following a cross-over study design it was possible to evaluate differences in plasma profiles between the two preparations, and to relate these to encountered side effects. All patients had previously been receiving neuroleptic treatment and had been diagnosed according to DSM-III. The dosage and intervals between injections were on an individual basis. The results indicate that at all dosage levels, the decanoate preparation showed significantly lower peak plasma concentrations of perphenazine. Extrapyramidal side effects and sedation were also less pronounced after the administration of PD. The more even and flat plasma concentrations obtained with PD, may facilitate plasma monitored therapy by using minimum concentration values.

Adult↗
PubMed1985

Chemotherapy with neuroleptics. Clinical and pharmacokinetic aspects with a particular view to depot preparations.

Attempting to improve long-term neuroleptic treatment of schizophrenic patients several injectable depot neuroleptics have been developed. Moreover pharmacokinetic data increasingly have been clinically applied. On this background the purpose of the present paper has been to make an updated review of the clinical and pharmacokinetic knowledge of depot neuroleptic treatment. First, general aspects of antipsychotics have been summarized, and an outline of methodological questions relevant to clinical-pharmacological trials are given. Subsequently general aspects including pros & cons of depot administration are examined. Finally the available data of the various depot preparations have been scrutinized. It is concluded that our present pharmacokinetic knowledge of the particular preparations is incomplete. Thus more information of clinical relevant aspects are needed, e.g., the existence of a therapeutic range, maximum/minimum concentration ratio, and the significance of active metabolites. Comparing the various depot neuroleptics, no significant differences are seen regarding the clinical effects. However, the decanoate esters seem clinical superior to the corresponding enanthate esters explained by the more flat concentration curve of the decanoates. Apart from that, a comparison of the pharmacokinetic data is difficult because of the heterogenecy of the available data. Haloperidol, clopenthixol and perphenazine decanoates are among the best examined preparations in pharmacokinetic respects. A controlled double-blind comparative study of these preparations would be of interest.

Administration, Oral↗
PubMed1985

Perphenazine decanoate vs. perphenazine enanthate: efficacy and side effects in a 6 week double-blind, comparative study of 50 drug monitored psychotic patients.

In a six-week randomized, double-blind study the efficacy and side effects of perphenazine decanoate (PD) and perphenazine enanthate (PE) were evaluated and compared in 26 and 24 acute psychotic patients respectively. Of either formulation 100 mg were administered intramuscularly every two weeks. Maximum and minimum plasma concentrations of perphenazine were measured for each injection period using gas liquid chromatography. There was no statistically significant difference between PD and PE in terms of overall antipsychotic efficacy, assessed by means of the Brief Psychiatric Rating Scale (BPRS). However, when an 'Amelioration Score' (AMS) of at least 50% of the totally obtainable scores was defined as individual response criterion it was revealed that the PD group only one patient (4%) did not meet this criterion, compared with six patients (25%) in the PE group. Extrapyramidal side effects were significantly more pronounced in the PE-treated patients, who also required significantly higher amounts of antiparkinson medication. The mean maximum concentration of perphenazine in plasma was 5.0 nmol/l in the PD, and 10.6 nmol/l in the PE-treated patients. The ratio of the mean maximum to the mean minimum concentration was 1.41 and 4.02 in the decanoate and enanthate groups respectively. In the patients treated with PD there were signs of accumulation indicating the possibility of prolonging dosage intervals. The present study yielded further support to previous findings demonstrating that intramuscular administration of PD dissolved in sesame oil, in contrast to PE, results in even and flat plasma perphenazine concentration curves, which not only provides a stable antipsychotic effect but also most likely carry the responsibility for the low incidence of extrapyramidal side effects observed.

Adult↗
PubMed1985

Long-term depot neuroleptic treatment with perphenazine decanoate. I. Efficacy and side effects in a 12 month study of 42 drug monitored psychotic patients.

In an open, prospective 12 month study of perphenazine decanoate (PD), 42 psychotic patients diagnosed according to DSM-III were treated with a fixed depot interval and an individual dose, guided by gas chromatographic perphenazine plasma concentration monitoring combined with clinical evaluation. Degree of illness was rated using a social-psychiatric CGI-scale and extrapyramidal side effects were evaluated by means of a modified Simpson and Angus rating scale. After six months of treatment, a statistically significant improvement was found (p less than 0.001). During the last six months a further slight reduction in mean CGI-scores was observed. Mild to moderate extrapyramidal side effects occurred in 9 patients (21%) principally during the initial phase of therapy. No other side effects or changes in blood chemistry were found during the study. Plasma concentrations of perphenazine increased during the initial 3 months and stabilized hereafter. There were however, large intra- and inter-individual variations in the perphenazine plasma concentration/dose ratio. In addition, it was observed that plasma concentrations of perphenazine were significantly higher in patients who had been treated with neuroleptics for more than 10 years compared to those who had been treated 5 years or less. This observation indicates gradual development of tolerance to neuroleptic treatment. This study demonstrates that PD is a safe and effective remedy for maintenance therapy in psychotic patients.

Adult↗
PubMed1985

Long-term depot neuroleptic treatment with perphenazine decanoate. II. Different depot intervals in the last 6 months of a 12 month study of 42 drug monitored psychotic patients.

In order to investigate the feasibility of administering perphenazine decanoate (PD) at three week intervals the 42 patients participating in the previously reported open, prospective 12 month study were, after six months, treated according to the following scheme: 21 patients continued to receive injections every two weeks (group I), whereas in the remaining 21 patients the intervals between injections were extended to 3 weeks (group II). Both groups continued to respond equally well to therapy. Moreover it was observed that the mean daily dose of perphenazine was significantly reduced when using 3 weeks intervals. This study demonstrates that PD administered every 3 weeks is a safe and effective remedy for maintenance therapy in psychotic patients.

Adult↗
PubMed1984

Cannabis and neuroleptic agents in schizophrenia.

A description is given of 10 schizophrenic patients whose condition was acutely aggravated following cannabis use, despite verified adequate depot treatment with neuroleptics. It is concluded that cannabis use constitutes a risk factor for schizophrenic patients, and the hypothesis is suggested that there may exist a cannabis-neuroleptics antagonistic interaction. Recent research in cannabis pharmacokinetics is presented in support of this hypothesis.

Adult↗
PubMed1984

Zimeldine versus nomifensine. A double-blind study of depressed inpatients.

A double-blind comparison of zimeldine, a selective 5-HT reuptake inhibitor, and nomifensine, a noradrenaline and a dopamine reuptake inhibitor, was carried out in 43 inpatients with a scheduled treatment period of 6 weeks. All patients were diagnosed as definite major depressive disorder according to Research Diagnostic Criteria (RDC), and the WHO International Classification of Diseases (ICD-9). The antidepressive efficacy was evaluated by a 10-item subscale of the Comprehensive Psychopathological Rating Scale (CPRS), a clinical global impression (CGI) scale and a self-rating scale (VAMS). Side effects were recorded, and anticholinergic effect was evaluated by parotid saliva volume measurement. No statistically significant differences in efficacy or profile between the two drugs were demonstrable. With the exception of increased sweating in the zimeldine group there were no statistically significant differences in side effects.

Bipolar Disorder↗
PubMed1983

L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase.

Column perifusion of collagenase-isolated mouse pancreatic islets was used to study the dynamics of insulin release in experiments lasting for several hours. The methyl esters of L-leucine and L-arginine were synthesized. Whereas L-arginine methyl ester (L-arginine OMe) had no effect, L-leucine OMe stimulated the release of insulin. The effect of L-leucine OMe was maximal at 5 mmol/liter. Whereas the Km for glucose-stimulated insulin release was unaffected by 1 mmol/liter L-leucine OMe, the maximal release of D-glucose was increased by the amino acid derivative that appeared more effective than L-leucine. L-Leucine OMe was also a potent stimulus of insulin release from the perfused mouse pancreas. In the presence of 10 mmol/liter L-glutamine, 1 mmol/liter L-leucine OMe induced a 50- to 75-fold increase in insulin release. A similar stimulatory effect was also observed in column-perifused RIN 5F cells, a cloned rat islet tumor cell line. A twofold increase in islet glutamate dehydrogenase activity was induced by 5 mmol/liter L-leucine OMe, a larger effect than that of L-leucine (P less than 0.02), whereas L-arginine OMe had a small inhibitory effect. We conclude that L-leucine OMe is a potent stimulus of insulin secretion and that its effect on the beta-cells may be exerted by activating islet glutamate dehydrogenase.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Inhibitory activity of antibodies to human Ia-like determinants: comparison of intact and pepsin-digested antibodies.

Antibodies which react with products encoded by the human DR locus precipitate a biomolecular membrane glycoprotein complex with m.w. of 29,000 and 34,000 daltons. Such antibodies are directed against HLA-DR Ia-like antigens found on human B cells and human monocytes and have been shown previously to inhibit a variety of in vitro cellular and humoral immune reactions. We have compared the in vitro effects of such antibodies on two assays of human immunity: antigen-specific proliferation and polyclonal immunoglobulin production. Intact IgG fractions of a rabbit heteroantiserum (anti-P29,34), a human MT-2 locus alloantiserum (Ia 172), and a mouse monoclonal antibody (LB 3.1) markedly inhibited in vitro immune reactivities of human mononuclear cells. Interestingly, F(ab')2 preparations of these antibodies failed to inhibit these in vitro immune responses at the concentrations tested. These data suggest that under certain conditions, Fc domains play a critical role in the inhibitory activity of antibodies to Ia-like molecules.

Animals↗
PubMed1978

Stability of rhodopsin in detergent solutions.

The thermal stability of lipid-free rhodopsin in solutions of a homologous series of alkyltrimethylammonium bromide detergents and one nonionic detergent, dodecyl-beta-maltoside, has been studied as a function of detergent concentration. Rhodopsin thermal stability increases with increasing chain length within the homologous series of ionic detergents, and for chain lengths greater than 10 carbon atoms increases with increasing detergent concentration up to a "critical" concentration that depends on the chain length. Stability also increases with increasing detergent concentration for rhodopsin in solutions of the nonionic detergent. These results may be rationalized in terms of the dependence of micelle packing density on the detergent chain length, head group, and concentration.

Animals↗